Hepatitis C virus (HCV) infection is a major health problem that leads to chronic liver disease, such as cirrhosis and hepatocellular carcinoma, in a substantial number of infected individuals, estimated to be 2-15% of the world's population.
The development of inhibitors of HCV NS5B polymerase with potential for the treatment of HCV infection has been reviewed in Poordad et al. (2012), supra; Asselah et al. (2009), supra; and Chatel-Chaix et al. Direct-acting and host-targeting HCV inhibitors: current and future directions. Current Opinion in Virology, 2:588-598 (2012). Nucleoside analogs that inhibit HCV NS5B polymerase are disclosed, for example, in WO 2011/035231, WO 2005/003147, WO 2010/0081628, U.S. Pat. No. 7,879,815, WO 2010/075517, WO 2010/002877, and WO 2009/132123.
Among these nucleoside analogs are prodrugs which have the 5′-OH group masked as a phosphoramidate moiety (also referred to as “McGuigan” prodrugs). See, for example, Bobeck et al., Antiviral Therapy, 15:935-950 (2010); and McGuigan et al., Bioorg Med Chem Lett, 20(16)4850-4854 (2010). U.S. Pat. No. 8,629,263 discloses reagents that can be used to add phosphoramidate groups onto nucleoside compounds to prepare McGuigan type prodrugs.